JP2023012305A - Vinyl ether compound and methods for producing aldehyde compound and carboxylate compound therefrom - Google Patents

Abstract

To provide a method for producing a (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound by using a short-process and industrially viable purification means without using a harmful reagent.SOLUTION: The present invention provides a novel vinyl ether compound represented by the following general formula (1) (in the formula, R1 represents a C1-15 univalent hydrocarbon group; and the wavy line represents an E body, a Z body, or a mixture thereof). Further, the present invention provides a method for producing 2,3,4,4-tetramethyl-1-cyclopentene carbaldehyde (2), comprising at least a step of obtaining 2,3,4,4-tetramethyl-1-cyclopentene carbaldehyde represented by the following formula (2) by subjecting the vinyl ether compound (1) to a hydrolysis reaction.SELECTED DRAWING: None

Description

The present invention relates to novel vinyl ether compounds. The present invention also provides from said vinyl ether compounds aldehyde compounds, namely 2,3,4,4-tetramethylcyclopentanecarbaldehyde and 2,3,4,4-tetramethylcyclopentanecarbaldehyde, and carboxylate compounds, namely (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound.

Insect sex pheromones are biologically active substances that normally have the function of attracting female individuals to male individuals, and exhibit high attractiveness even in small amounts. Sex pheromones are widely used as a means of predicting outbreaks, confirming geographical spread (invasion into specific areas), and as a means of pest control. Pest control means include mass trapping, lure and kill or attract and kill, lure and infect or attract and infect, and mating disruption. Control methods are widely put into practical use. Since the amount of sex pheromone that can be extracted from an individual insect is extremely small, it is difficult to use naturally derived sex pheromone for communication disruption, etc. Therefore, when using sex pheromone, the necessary amount of raw material for sex pheromone is artificially produced. is needed for basic research as well as for applications.

Pseudococcus viburni (common name: Obsucure Mealybug, hereinafter abbreviated as "OMB") is mainly distributed in the Americas and damages various crops including grapes, so it is economically very important. pests. In recent years, the distribution of OMB has spread, and confirmation of geographical diffusion has become important. The sex pheromone of OMB is reported to be (2,3,4,4-tetramethylcyclopentyl)methyl acetate, one of the (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compounds. (Non-Patent Document 1 below). In addition, in a male attraction test using the synthesized racemate of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate, the synthetic product was found to be a natural pheromone. It has been reported that they exhibit equivalent attractant activity (Non-Patent Document 1).

An example of synthesizing OMB sex pheromones is synthesis using isobutyl methacrylate as a starting material and Nazarov cyclization reaction (Non-Patent Document 1). An improved synthesis method of Non-Patent Document 1 has also been reported (Non-Patent Documents 2 and 3 below). Thus, a methylenation reaction of ketones with dibromomethane, zinc and titanium(IV) chloride is used to improve the yield. Furthermore, synthesis of an optically active substance using (-)-pantolactone as a starting material and a key tandem conjugate addition-cycloaddition reaction has also been reported (Non-Patent Document 4 below). As a production method intended for industrial production, Wakamori et al. have disclosed a method utilizing the Favorskii rearrangement reaction of α-halotetramethylcyclohexanone (Patent Document 1 below).

JP 2017-210469 A

J. Millar et al., J. Chem. Ecol. , 31, 2999 (2005) J. Millar et al., Tetrahedron Lett. , 48, 6377 (2007) J. Millar et al., Tetrahedron Lett. , 52, 4224 (2011) D. Reddy et al., Tetrahedron Lett. , 51, 5291 (2010) Bull. Soc. Chim. Fr. , 2981 (1970) and J. Am. Am. Chem. Soc. , 113, 8062 (1991)

However, although the synthesis method described in Non-Patent Document 1 is a short process, gas chromatography fractionation is used to purify the target product (2,3,4,4-tetramethylcyclopentyl)methyl acetate. Therefore, large-scale synthesis of (2,3,4,4-tetramethylcyclopentyl)methyl acetate is accompanied by great difficulty. In addition, the synthetic methods described in Non-Patent Documents 2 and 3 require the use of mutagenic dibromomethane and an oxidation reaction using highly toxic hexavalent chromium. It is difficult to implement on an industrial scale because it requires a silica gel column chromatography method that is expensive and difficult to scale up. Furthermore, in Non-Patent Document 4, synthesis of the target product (2,3,4,4-tetramethylcyclopentyl)methyl acetate requires as many as 17 steps from (−)-pantolactone, and conjugation Due to the extremely low temperature of −78° C. used for the addition reaction and the highly explosive high-valence iodine reagent used for the oxidation reaction, it is difficult to implement on an industrial scale.

On the other hand, Patent Document 1 describes a more industrial synthesis method, but there has been a demand for a more regioselective production method than the Favorsky rearrangement reaction.

As described above, in the conventional production method, a sufficient amount of (2,3,4,4-tetramethyl It was thought that industrial production of cyclopentyl)methyl acetate was extremely difficult, and that there was room for improvement in reaction selectivity.

The present invention has been made in view of the above circumstances, and uses a short process and an industrially feasible purification means without using harmful reagents to produce (2,3,4,4-tetramethylcyclopentyl)methyl=carboxyl. It is an object of the present invention to provide a method for producing rate compounds.

In addition, based on the attractant activity of the racemate, a sufficient amount of OMB sex pheromone (2,3,4,4-tetramethyl It is also an object to provide a process for preparing the racemate of cyclopentyl)methyl acetate. More preferably, (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl)-methyl=acetate with a diastereomeric ratio (dr) of 50% or more. . Here, the diastereomer ratio (dr) is the number of moles of one diastereomer of interest divided by the total number of moles of all diastereomers present, expressed in %.

As a result of extensive studies, the present inventors have found that a novel compound, a vinyl ether compound and an aldehyde compound, namely 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde, is a carboxylate compound, namely ( 2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compounds.

In addition, as a result of extensive studies, the present inventors have found that by going through the above two intermediates, it is possible to industrially (2,3,4,4- It has been found that tetramethylcyclopentyl)methyl carboxylate compounds can be prepared.

Furthermore, as a result of extensive studies, the present inventors have found that (2,3,4,4-tetramethylcyclopentyl)methyl acetate can be produced in the racemate, and (2,3,4,4- Among the four diastereomers of tetramethylcyclopentyl)methyl acetate, (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetra- It was found that the diastereomeric ratio (dr) of methylcyclopentyl)methyl acetate can be 50% or more.

（上記一般式（１）中、Ｒ^１は炭素数１～１５の一価の炭化水素基を表し、波線はＥ体、Ｚ体又はそれらの混合物であることを表す。） According to one aspect of the present invention, 2,3,4,4-tetramethyl represented by the following formula (2) is obtained by subjecting a vinyl ether compound represented by the following general formula (1) to a hydrolysis reaction. A method for producing 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) can be provided, comprising at least a step of obtaining -1-cyclopentenecarbaldehyde.

(In general formula (1) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and the wavy line represents the E form, Z form, or a mixture thereof.)

Further, according to another aspect of the present invention, the method for producing 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) and the 2,3,4,4-tetramethyl- 2,3, comprising at least a step of obtaining 2,3,4,4-tetramethylcyclopentanecarbaldehyde represented by the following formula (3) by subjecting 1-cyclopentenecarbaldehyde (2) to a hydrogenation reaction; ,4,4-tetramethylcyclopentanecarbaldehyde (3).

（上記一般式（５）中、Ｒ^２は水素原子又は炭素数１～１５の一価の炭化水素基を表す。） Furthermore, according to another aspect of the present invention, the method for producing the above 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) and the 2,3,4,4-tetramethylcyclopentanecarbaldehyde a step of obtaining (2,3,4,4-tetramethylcyclopentyl)methanol represented by the following formula (4) by subjecting rudehyde (3) to a reduction reaction with a reducing agent; ,4,4-tetramethylcyclopentyl)methanol (4) is subjected to an esterification reaction to give a (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound represented by the following general formula (5): (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) can be provided.

(In general formula (5) above, R ² represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 15 carbon atoms.)

（上記式（５Ａ）及び（５Ａ’）中、Ａｃはアセチル基を表し、（Ｒ^＊）、（Ｓ^＊）、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表し、以下同じである。） Further, according to another aspect of the present invention, the carboxylate compound (5) is (2,3,4,4-tetramethylcyclopentyl)methyl=acetate represented by the following formula (5A), In (2,3,4,4-tetramethylcyclopentyl)methyl acetate, among the four diastereomers, (1R ^* ,2R ^* ,3S ^* )-(2) represented by the following formula (5A′) (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) having a diastereomeric ratio (dr) of 50% or more in ,3,4,4-tetramethylcyclopentyl)methyl acetate can provide a manufacturing method of

(In formulas (5A) and (5A′) above, Ac represents an acetyl group, (R ^* ), (S ^* ), bold bonds and hashed bonds represent relative configurations, The same shall apply hereinafter.)

（上記一般式（７）中、Ｒ^１は炭素数１～１５の一価の炭化水素基を表し、Ｐｈはフェニル基を表す。） Furthermore, according to another aspect of the present invention, 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and a phosphorus ylide represented by the following general formula (7) 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) above, further comprising the step of obtaining the vinyl ether compound (1) by subjecting the compound to a Wittig reaction, A method for preparing 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) or the (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) above can be provided.

(In general formula (7) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and Ph represents a phenyl group.)

（式中、Ｒ^１は炭素数１～１５の一価の炭化水素基であり、波線はＥ体、Ｚ体又はそれらの混合物であることを表す。） Further, according to another aspect of the present invention, it is possible to provide a vinyl ether compound represented by the following general formula (1).

(In the formula, R ¹ is a monovalent hydrocarbon group having 1 to 15 carbon atoms, and the wavy line represents the E form, Z form, or a mixture thereof.)

Furthermore, according to another aspect of the present invention, 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde represented by the following formula (2) can be provided.

According to the present invention, a (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound, in particular, as a sex pheromone for OMB, which is an important agricultural pest, is expected to be applied to prediction of outbreaks and control. (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate can be produced safely, efficiently, selectively and industrially. Further, according to the present invention, the above vinyl ether compound (1) and the above 2,3,4,4, which are useful intermediates for the production of (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compounds -tetramethyl-1-cyclopentenecarbaldehyde (2) can also be provided.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to these. In addition, in the chemical formulas of intermediates, reagents and target products in this specification, there may be stereoisomers such as enantiomers or diastereoisomers due to the structure, but unless otherwise specified, any Each chemical formula also represents all of these isomers. Also, these isomers may be used singly or as a mixture.

As explained below, the present inventors considered a plan for synthesizing the target compound (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5).
The reaction formula of the retrosynthetic analysis below is the racemic OMB pheromone (1R ^* , 2R ^* , 3S ^* ) of the (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5). )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A′) is shown as an example.

（上式中、Ｒ^１は炭素数１～１５の一価の炭化水素基を表し、波線はＥ体、Ｚ体又はそれらの混合物であることを表し、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表す。）

(In the above formula, R ¹ represents a monovalent hydrocarbon group with 1 to 15 carbon atoms, the wavy line represents the E form, Z form or a mixture thereof, bold bond and hash bond hashed bond) represents the relative configuration.)

In the reaction formula of the above retrosynthetic analysis, the white arrows represent transforms in the retrosynthetic analysis.

(Process D')
The above (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A') is 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3 ), it was thought possible to synthesize from (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde represented by the formula (3′). Specifically, 1) If necessary, (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) is stereoisomerized at the 1-position (epimation (epimerization)), 2) reduction of the aldehyde to an alcohol, and 3) esterification of the alcohol.

(Process C')
(1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) is 2,3,4,4-tetramethyl-1 represented by formula (2). - Cyclopentenecarbaldehyde was considered to be synthesizable by subjecting it to a reduction reaction, preferably a hydrogenation reaction to the double bond. Addition of hydrogen to the 2-position from the more open face of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2), ie the face opposite the methyl group at the 3-position, leads to 2,3 It was expected that the cis form with the desired configuration for the dimethyl group at the position would be preferentially produced. Also, if (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) affords the 2,3-cis configuration, subsequent transformations can lead to stereoisomeric The desired 2,3-cis configuration is retained all the way to the target compound without fear of . Therefore, the above 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) is selected as a substrate, and then the hydrogenation reaction to the double bond, which is expected to undergo stereoselective hydrogenation, is carried out. It is extremely important to do so. In general, hydrogenation reactions can be carried out using very inexpensive molecular hydrogen and a small amount of reusable hydrogenation catalyst, which is advantageous from the viewpoint of industrial economy.

(Process B')
It was thought that 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) could be synthesized by hydrolyzing the vinyl ether compound represented by general formula (1). When an aldehyde is produced in the hydrolysis of the vinyl ether compound (1), the double bond in the ring is thermodynamically more stable due to conjugation with the carbonyl group of the aldehyde, and the 2, It was thought that isomerization easily occurred from between the 3-positions.

(Process A')
The vinyl ether compound (1) is a known ketone and includes 2,3,4,4-tetramethyl-2-cyclopentenone represented by formula (6) and a phosphorus ylide compound represented by formula (7). could be synthesized by subjecting it to the Wittig reaction.

Considering the reaction formula of the above retrosynthetic analysis, the chemical reaction formula according to one embodiment of the present invention is shown as follows.

(Step A) As shown in the above chemical reaction formula, by subjecting 2,3,4,4-tetramethyl-2-cyclopentenone (6) and phosphorus ylide compound (7) to Wittig reaction , the vinyl ether compound (1) is obtained.
(Step B) Next, the vinyl ether compound (1) obtained according to Step A is hydrolyzed to obtain 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2).
(Step C) 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) obtained according to Step B is hydrogenated to give 2,3,4,4-tetramethylcyclopentane. Carbaldehyde (3) is obtained.
(Step D) 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) to 1) optionally 1-position of 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) , 2) reduction of the aldehyde to an alcohol, and 3) esterification of the alcohol to give the target compound (2,3,4,4-tetramethylcyclopentyl)methyl = carboxylate compound (5) is obtained.

Hereinafter, as an example of the embodiment of the present invention, Steps A to D based on the retrosynthetic analysis will be described in detail in the order of Step B, Step A, Step C, and Step D.

（上記一般式中、Ｒ^１は上記で定義した通りであり、波線は、Ｅ体、Ｚ体又はそれらの混合物であることを表す。） [1] Step B
Step B for obtaining 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) represented by the following general formula (2) will be described below. 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) is obtained by subjecting a vinyl ether compound represented by the following general formula (1) to hydrolysis, as shown in the chemical reaction formula below. obtained by

(In the general formula above, R ¹ is as defined above, and the wavy line represents the E form, Z form, or a mixture thereof.)

First, the vinyl ether compound represented by the following general formula (1), which is the starting material in step B, will be described.

In general formula (1), R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 7 carbon atoms, more preferably 1 to 4 carbon atoms; Represents a mixture.
Monovalent hydrocarbon groups include linear saturated hydrocarbon groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, decyl, undecyl and pentadecyl; isopropyl, s branched saturated hydrocarbon groups such as -butyl group, t-butyl group and isobutyl group; cyclic saturated hydrocarbon groups such as cyclohexyl group; and unsaturated hydrocarbon groups such as allyl group; aryl groups such as phenyl group and aralkyl groups such as a benzyl group and a phenethyl group, with methyl, ethyl, phenyl and benzyl being particularly preferred from the viewpoint of economy. In addition, some of the hydrogen atoms of these hydrocarbon groups may be substituted, and in that case, the substituent is preferably a halogen group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group or a trialkylsilyl group. , more specific examples of substituted hydrocarbon groups include 2-(trimethylsilyl)ethyl, 2-methoxyethyl, 2-(methylthio)ethyl, chlorophenyl and methoxyphenyl groups.

Specific examples of the vinyl ether compound (1) include 4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(ethoxymethylene)-1,1,2,3-tetra methyl-2-cyclopentene, 4-(propoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(butoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(pentadecyloxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(isopropoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-( cyclohexyloxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(allyloxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(phenoxymethylene)- 1,1,2,3-tetramethyl-2-cyclopentene, 4-(benzyloxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-[2-(trimethylsilyl)ethoxymethylene]- 1,1,2,3-tetramethyl-2-cyclopentene, 4-[(2-methoxyethoxy)methylene]-1,1,2,3-tetramethyl-2-cyclopentene, 4-[2-(methylthio) ethoxymethylene]-1,1,2,3-tetramethyl-2-cyclopentene, 4-[(4-chlorophenoxy)methylene]-1,1,2,3-tetramethyl-2-cyclopentene and 4-[( 4-Methoxyphenoxy)methylene]-1,1,2,3-tetramethyl-2-cyclopentene, and 4-(methoxymethylene)-1,1,2 ,3-tetramethyl-2-cyclopentene, 4-(ethoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene, 4-(phenoxymethylene)-1,1,2,3-tetramethyl- 2-cyclopentene, 4-(benzyloxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene are preferred.
The method for producing the vinyl ether compound (1) will be described in step A below.

Next, 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2), which is the target substance in step B, is represented by the following formula (2).

The above hydrolysis reaction can be carried out by adding water and, if necessary, an acid and/or a solvent to the vinyl ether compound (1). Also, the hydrogenation reaction may be carried out while cooling or heating.

The amount of water used in the hydrolysis reaction can be set arbitrarily as long as a practically sufficient reaction rate is obtained. It is more preferably 0.5 to 10,000 mol, still more preferably 1 to 1,000 mol.

The acid used in the hydrolysis reaction is preferably a commercially available acid that is available in large quantities, such as inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid and phosphoric acid, or salts thereof; , organic acids such as acetic acid, propionic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid and naphthalenesulfonic acid, or salts thereof; lithium tetrafluoroborate, Boron trifluoride, boron trichloride, boron tribromide, aluminum trichloride, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, tin dichloride, titanium tetrachloride, titanium tetrabromide and trimethylsilyl-iodide; oxides such as alumina, silica gel and titania; various cation exchange resins; and minerals such as montmorillonite. Hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, oxalic acid and p-toluenesulfonic acid are preferred from the viewpoint of economy and/or reactivity.
The acid may be used alone or in combination of two or more. In addition, as the acid, a commercially available one can be used.

The amount of the acid used can be set arbitrarily as long as a practically sufficient reaction rate is obtained, but from the viewpoint of economy, it is preferably as small as possible, and preferably 0 per 1 mol of the vinyl ether compound (1). 0.00001 to 10,000 mol, more preferably 0.0001 to 1,000 mol, still more preferably 0.001 to 100 mol.

A solvent other than water may be used for the hydrolysis reaction.
Examples of the solvent include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; methylene chloride, chloroform and trichlorethylene. chlorinated solvents such as; acetone, ketones such as methyl = ethyl ketone; N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO) and hexamethylphosphoric triamide (HMPA); nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and methanol, ethanol and t-butyl = alcohols such as alcohol, preferably ethers such as diethyl ether and tetrahydrofuran, or a mixed solvent containing the ethers.
The solvent may be used alone or in combination of two or more. Also, as the solvent, a commercially available one can be used.
The amount of the solvent to be used is preferably 10 g to 10,000 g per 1 mol of the vinyl ether compound (1).

The reaction temperature of the hydrolysis reaction is preferably -78 to 160°C, more preferably -50 to 140°C, still more preferably -30 to 120°C, depending on the reaction conditions.
The reaction time of the hydrolysis reaction can be set arbitrarily, but the reaction can be completed by following the reaction using gas chromatography (GC) and/or silica gel thin layer chromatography (TLC). It is preferable from the viewpoint of rate, and usually 0.5 to 100 hours is preferable.

When the hydrolysis of the vinyl ether compound (1) produces an aldehyde, the originally double bond at the 2-position readily isomerizes to the 1-position, which is thermodynamically more stable, by conjugation with the carbonyl group of the aldehyde, and 2 , 3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2).

In the hydrolysis reaction, the reaction by-product alcohol R ¹ OH and the starting vinyl ether compound (1) or the product 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde ( The reaction with 2) may produce an undesired acetal compound as a by-product. In that case, the hydrolysis reaction may be carried out while removing the alcohol R ¹ OH produced by the reaction from the reaction system by a method such as distillation in order to suppress the unwanted by-production of the acetal compound. .

When 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) obtained by the hydrolysis reaction has sufficient purity for use in the next step, It may be used in the next step as it is or as a filtered reaction solution. Alternatively, if you want to separate and remove impurities such as positional isomers of double bonds that may be mixed, purify by appropriately selecting from purification methods in ordinary organic synthesis such as distillation and / or various chromatography. good too. When purification is carried out, distillation, for example, distillation under reduced pressure is particularly preferred from the viewpoint of industrial economy.

（上記一般式中、Ｒ^１は炭素数１～１５の一価の炭化水素基を示す。Ｐｈはフェニル基を表す。波線は、Ｅ体、Ｚ体又はそれらの混合物であることを表す） [2] Step A
The process A for obtaining the vinyl ether compound represented by the following general formula (1) will be described below. The vinyl ether compound (1) comprises 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and the following formula ( It is obtained by subjecting the phosphorus ylide compound (7) represented by 7) to Wittig reaction.

(In the general formula above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms. Ph represents a phenyl group. A wavy line represents an E form, a Z form or a mixture thereof.)

The starting material for step A, 2,3,4,4-tetramethyl-2-cyclopentenone (6), is a known compound and is described, for example, in Bull. Soc. Chim. Fr. , 2981 (1970) or J. Am. Am. Chem. Soc. , 113, 8062 (1991).

Next, the phosphorus ylide compound (7) will be explained below.

R ¹ in general formula (7) is as defined in general formula (1) above.
Specific examples of the phosphorus ylide compound (7) include (methoxymethylene)triphenylphosphorane, (ethoxymethylene)triphenylphosphorane, (propoxymethylene)triphenylphosphorane, (butoxymethylene)triphenylphosphorane, (decyl oxymethylene)triphenylphosphorane, (pentadecyloxymethylene)triphenylphosphorane, (isopropoxymethylene)triphenylphosphorane, (cyclohexyloxymethylene)triphenylphosphorane, (allyloxymethylene)triphenylphosphorane, ( phenoxymethylene)triphenylphosphorane, (benzyloxymethylene)triphenylphosphorane, triphenyl[2-(trimethylsilyl)ethoxymethylene]phosphorane, [(2-methoxyethoxy)methylene]triphenylphosphorane, [2-(methylthio ) ethoxymethylene]triphenylphosphorane, [(4-chlorophenoxy)methylene]triphenylphosphorane and [(4-methoxyphenoxy)methylene]triphenylphosphorane, etc. From the viewpoint, (methoxymethylene)triphenylphosphorane, (ethoxymethylene)triphenylphosphorane, (phenoxymethylene)triphenylphosphorane, (benzyloxymethylene)triphenylphosphorane and the like are preferable.

The method for producing the phosphorus ylide compound (7) is not particularly limited. Obtained by hydrogenation reaction.

In the general formula above, R ¹ is as defined in general formula (1) above. X represents a halogen atom, preferably a chlorine atom, a bromine atom or an iodine atom. Ph represents a phenyl group.

R ¹ in general formula (101) is as defined in general formula (1) above. X is a halogen atom, preferably a chlorine atom, a bromine atom or an iodine atom. Specific examples of the triphenylphosphonium halide compound (101) include (methoxymethyl)triphenylphosphonium chloride, (methoxymethyl)triphenylphosphonium bromide, (methoxymethyltriphenylphosphonium)iodide, and (ethoxymethyl)triphenylphosphonium chloride. , (butoxymethyl)triphenylphosphonium chloride, (pentadecyloxymethyl)triphenylphosphonium chloride, (isopropoxymethyl)triphenylphosphonium chloride, (cyclohexyloxymethyl)triphenylphosphonium chloride, (allyloxymethyl)triphenylphosphonium chloride , (phenoxymethyl)triphenylphosphonium chloride, (benzyloxymethyl)triphenylphosphonium chloride, triphenyl[2-(trimethylsilyl)ethoxymethylene]phosphonium chloride, [(2-methoxyethoxy)methyl)triphenylphosphonium chloride, [2 -(methylthio)ethoxymethyl)triphenylphosphonium chloride, [(4-chlorophenoxy)methyl)triphenylphosphonium chloride and [(4-methoxyphenoxy)methyl)triphenylphosphonium chloride and the like.
A commercially available triphenylphosphonium halide compound (101) may be used, or a quaternary phosphonium reaction of a halide represented by the following general formula (102), triphenylphosphine, and (PPh ₃ ) may be prepared by

（上記一般式中、Ｒ^１、Ｘ及びＰｈは上記で定義した通りである。）

(In the above general formula, R ¹ , X and Ph are as defined above.)

Specific examples of halide (102) include chloromethyl=methyl=ether, bromomethyl=methyl=ether, iodomethyl=methyl=ether, chloromethyl=ethyl=ether, butyl=chloromethyl=ether, chloromethyl=pentadecyl=ether. , chloromethyl isopropyl ether, cyclohexyl chloromethyl ether, allyl chloromethyl ether, chloromethyl phenyl ether, benzyl chloromethyl ether, 2-methoxyethoxymethyl chloride, chloromethyl 2-(trimethylsilyl ) ethyl=ether, chloromethyl=2-(methylthio)ethoxymethyl=ether, chloromethyl=4-chlorophenyl=ether and chloromethyl=4-methoxyphenyl=ether and the like.

In preparing the triphenylphosphonium halide compound (101), a metal halide and/or a quaternary onium salt may be added to accelerate the reaction.
Examples of the metal halide include lithium iodide, sodium iodide, potassium iodide, lithium bromide, sodium bromide, potassium bromide and the like.
The quaternary onium salts include tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylphosphonium bromide, tetraethylammonium iodide, tetrabutylammonium iodide and tetrabutylphosphonium iodide.

Further, when preparing the triphenylphosphonium halide compound (101), lithium hydrogen carbonate, hydrogen carbonate such as sodium hydrogen carbonate or potassium hydrogen carbonate, carbonate such as lithium carbonate, sodium carbonate or potassium carbonate, lithium hydroxide, Hydroxide salts such as sodium hydroxide or potassium hydroxide; or triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine, quinoline, pyrrolidine, Organic bases such as piperidine, collidine, lutidine or morpholine may be added to react on the basic side.

Preparation of the triphenylphosphonium halide compound (101) is preferably carried out in a solvent.
Examples of the solvent include ethers such as diethyl ether, dibutyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; methylene chloride, chloroform and trichlorethylene. Chlorine-based solvents such as; aprotic polar solvents; nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and n-butyl acetate; and alcohols such as methanol, ethanol and t-butyl alcohol. Or they can be mixed and used.
The amount of the solvent to be used is preferably 10 g to 10,000 g per 1 mol of halide (102).

Regarding the reaction temperature for preparing the triphenylphosphonium halide compound (101), suitable conditions can be selected depending on the raw materials used, but it is usually -10°C to 180°C, preferably 0°C to 160°C, more preferably 10°C. It is preferred to work at ~140°C.
The reaction time for the preparation of the triphenylphosphonium halide compound (101) can be set arbitrarily. is desirable from the viewpoint of yield, and usually 0.5 to 60 hours is preferred.

Examples of the base used in the preparation of the phosphorus ylide compound (7) include sodium = methoxide, sodium = ethoxide, sodium = t-butoxide, sodium = t-amyloxide, lithium = methoxide, lithium = ethoxide, lithium = t-butoxide, Metal alkoxides such as lithium = t-amyloxide, potassium = methoxide, potassium = ethoxide, potassium = t-butoxide and potassium = t-amyloxide; methyllithium, ethyllithium, n-butyllithium, methylmagnesium chloride, sodium = acetylide and Organometallic reagents such as dimsyl sodium; sodium amide, lithium amide, lithium diisopropylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide and lithium dicyclohexylamide and metal hydrides such as sodium hydride, potassium hydride and calcium hydride.
One type or two or more types of the base may be used as needed, and the type and/or reactivity and/or reaction yield of the triphenylphosphonium halide compound (101) as a substrate are taken into consideration. can be selected. In addition, as the base, a commercially available one can be used.

The amount of the base used in the preparation of the phosphorus ylide compound (7) is preferably 0.7 mol to 5 mol per 1 mol of the triphenylphosphonium halide compound (101).
As the solvent used for preparing the phosphorus ylide compound (7), the same solvent as used for preparing the triphenylphosphonium halide compound (101) can be used.

The reaction temperature in the preparation of the phosphorus ylide compound (7) is preferably -78°C to 50°C, more preferably -78°C to 35°C.
The reaction time in the preparation of the phosphorus ylide compound (7) is preferably 5 minutes to 18 hours, more preferably 5 minutes to 10 hours considering the stability of the reagent.

Next, the vinyl ether compound (1), which is the target substance in step A, is as described in the above [1].

The above Wittig reaction can be carried out by adding 2,3,4,4-tetramethyl-2-cyclopentenone (6) in a solvent. Also, the Wittig reaction may be performed while cooling or heating.

The amount of 2,3,4,4-tetramethyl-2-cyclopentenone (6) used in the Wittig reaction is 0.1 mol to 5 mol per 1 mol of the theoretical phosphorus ylide compound (7). mol, preferably 0.2 mol to 3 mol.

As the solvent in the Wittig reaction, the same solvent as in the preparation of the triphenylphosphonium halide compound (101) can be used.
The amount of the solvent used in the Wittig reaction is preferably 10 g to 10,000 g per 1 mol of the theoretical amount of the phosphorus ylide compound (7).

The reaction temperature of the Wittig reaction is preferably -78°C to 50°C, more preferably -50°C to 35°C.
The reaction time of the Wittig reaction can be set arbitrarily. from the point of view, and usually 0.5 to 24 hours is preferred.

When the vinyl ether compound (1) obtained in the Wittig reaction has sufficient purity to be subjected to the next step, the following is performed as a crude product, as a reaction solution, or as a filtered reaction solution. You may use it for a process. Alternatively, when it is desired to separate and remove impurities, purification may be performed by appropriately selecting from purification methods in ordinary organic synthesis such as distillation and/or various chromatography. When purification is carried out, distillation, for example, distillation under reduced pressure is particularly preferred from the viewpoint of industrial economy.

The vinyl ether compound (1) obtained in the Wittig reaction has two geometric isomers, E-isomer and Z-isomer, due to the geometrical isomerism of the exocyclic double bond. Therefore, the vinyl ether compound (1) usually exists as a mixture of two types, but the mixture can be used in the next step as it is without the need to separate the geometric isomers.

[3] Process C
Step C for obtaining 2,3,4,4-tetramethylcyclopentanecarbaldehyde represented by the following formula (3) will be described below. The 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) is the 2,3,4,4-tetramethyl-1 obtained in Step B, as shown in the chemical reaction scheme below. -obtained by subjecting cyclopentenecarbaldehyde (2) to a hydrogenation reaction.

2,3,4,4-Tetramethyl-1-cyclopentenecarbaldehyde (2), which is the starting material of Step C, is as described in [1] above.

Next, the following 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3), which is the target substance in Step C, will be described below.

（上記式（３）中、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表す。） 2,3,4,4-Tetramethylcyclopentanecarbaldehyde (3) exists in four diastereomers, as follows: (1R ^* ,2R ^* ,3R ^* )-2,3 ,4,4-tetramethylcyclopentanecarbaldehyde (hereinafter also referred to as (1R ^* ,2R ^* ,3R ^* )-body); (1R ^* ,2S ^* ,3R ^* )-2,3,4,4-tetra methylcyclopentanecarbaldehyde (hereinafter also referred to as (1R ^* ,2S ^* ,3R ^* )-body); (1R ^* ,2S ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde ( hereinafter also referred to as (1R ^* ,2S ^* ,3S ^* )-body); and (1R ^* ,2R ^* ,3S ^* )-2,3,4,4-tetra Methylcyclopentanecarbaldehyde (hereinafter also referred to as (1R ^* ,2R ^* ,3S ^* )-form (3″)). The (1R ^* ,2R ^* ,3S ^* )-body (3″) has the same relative configuration as the OMB sex pheromone.

(In formula (3) above, bold bonds and hashed bonds represent relative configurations.)

The above hydrogenation reaction can be carried out by adding a hydrogenation catalyst and, if necessary, a solvent to the 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) and reacting with hydrogen. can. Also, the hydrogenation reaction may be carried out while cooling or heating.

The hydrogenation catalyst includes, for example, metals such as cobalt, nickel, rhodium, palladium, ruthenium, osmium, platinum, iridium, copper and iron (also referred to as metal catalysts), and metal oxides containing these metals (metal oxide catalysts metal hydroxides such as palladium hydroxide and rhodium hydroxide; metal halides such as palladium chloride, ruthenium chloride and rhodium chloride; and complex compounds such as chloroplatinic acid and chlorotris(triphenylphosphine) rhodium. is mentioned.
As the hydrogenation catalyst, the above-exemplified metal catalyst or metal oxide catalyst may be supported on a carrier. Examples of the carrier in that case include carbon, alumina, zeolite and silica gel. Carbon is preferred as the carrier, and specific examples of carbon as the carrier include rhodium on carbon, palladium on carbon, ruthenium on carbon, platinum on carbon and palladium hydroxide on carbon. Particularly preferred are rhodium on carbon, palladium on carbon and palladium hydroxide on carbon.
The hydrogenation catalyst may be used alone or in combination of two or more. In addition, a commercially available one can be used as the hydrogenation catalyst.

The amount of the hydrogenation catalyst used can be set arbitrarily as long as a practically sufficient reaction rate can be obtained, but from the viewpoint of economy, it is preferably as small as possible, and the 2,3,4,4-tetramethyl-1 It is preferably 0.00001 to 10 mol, more preferably 0.00001 to 1 mol, still more preferably 0.00001 to 0.5 mol, per 1 mol of -cyclopentenecarbaldehyde (2).

Examples of solvents in the hydrogenation reaction include alcohols such as methanol, ethanol, isopropyl alcohol, t-butyl alcohol, benzyl alcohol, methoxyethanol, ethoxyethanol, diethylene glycol=monomethyl=ether and triethylene glycol=monomethyl=ether; Ethers such as diethyl ether, di-n-butyl ether, tetrahydrofuran and 1,4-dioxane; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; N,N-dimethylformamide (DMF) , 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO) and hexamethylphosphoric triamide (HMPA); nitriles such as acetonitrile and propionitrile; carboxylic acids such as formic acid, acetic acid and trifluoroacetic acid; and water.
The solvent may be used alone or in combination of two or more. Also, as the solvent, a commercially available one can be used.

The amount of the solvent used is preferably 0.01 parts by mass to 100,000 parts by mass, more preferably 100 parts by mass of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2). is 0.1 to 10,000 parts by mass.

The hydrogen pressure in the hydrogenation reaction is preferably normal pressure to 5 MPa.
The reaction temperature of the hydrogenation reaction can be set arbitrarily as long as a practically sufficient reaction rate is obtained, but it is preferably -20°C to 150°C, more preferably 0°C to 100°C.
The reaction time of the hydrogenation reaction can be set arbitrarily. from the point of view, and usually 5 minutes to 240 hours.

When the 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) obtained by the hydrogenation reaction has sufficient purity for use in the next step, it is used as a crude product, or The reaction solution or the filtered reaction solution may be directly used in the next step. Alternatively, when it is desired to separate and remove impurities, purification may be performed by appropriately selecting from purification methods in ordinary organic synthesis such as distillation and/or various chromatography. When purification is carried out, distillation, for example, distillation under reduced pressure is particularly preferred from the viewpoint of industrial economy.

In the case of producing racemic OMB pheromone (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A'), it is represented by the following formula. , 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) is represented by the following formula (3′), in which the dimethyl groups at the 2- and 3-positions are cis-configured (1RS, 2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) (hereinafter also referred to as (1RS,2R ^* ,3S ^* )-form (3′)) and 2-position (1RS,2S ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) (hereinafter, (1RS,2S ^* ,3S ^* )-form), (1RS,2R ^* ,3S ^* )-form (3') is preferred.

In order to preferentially produce the (1RS,2R ^* ,3S ^* )-body (3'), the hydrogenation catalyst is a metal such as rhodium or palladium, a metal oxide containing these metals, or a metal oxide containing these metals. A catalyst or a metal oxidation catalyst supported on a carrier such as carbon, alumina, zeolite, or silica gel is preferably used, and carbon is particularly preferred. Specifically, rhodium = carbon, palladium = carbon, and palladium hydroxide = carbon. It is even more particularly preferred to use In general, in the hydrogenation reaction using these hydrogenation catalysts, hydrogen atoms are easily added from the sterically vacant surface of the substrate molecule. , 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) is hydrogenated preferentially from the more open face, ie, the face opposite the 3-methyl group, to give the desired 2,3- It is believed that the cis configuration is preferentially obtained. In addition, since the relative configuration of the 2,3-dimethyl group of the (1RS,2R ^* ,3S ^* )-body (3′) obtained in step C is maintained until the final product in the subsequent steps, step C It is very important to improve the diastereomeric ratio of the target product to increase the stereoselectivity at .

[4] Process D
Step D for obtaining a (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound represented by the following general formula (5) will be described below. The (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) is the 2,3,4,4- (2,3,4,4-tetramethylcyclopentyl)methanol represented by the following formula (4) is obtained by subjecting tetramethylcyclopentanecarbaldehyde (3) to a reduction reaction with a reducing agent, and Next, the obtained (2,3,4,4-tetramethylcyclopentyl)methanol (4) is subjected to an esterification reaction to obtain.

2,3,4,4-Tetramethylcyclopentanecarbaldehyde (3), which is the starting material for Step D, is as described in [3] above.

(2,3,4,4-tetramethylcyclopentyl)methanol, which is an intermediate in step D, is represented by the following formula (4).

（上記式（４）中、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表す。） (2,3,4,4-Tetramethylcyclopentyl)methanol (4) exists in four diastereomers, as follows: (1R ^* , 2R ^* , 3R ^* )-(2, 3,4,4-tetramethylcyclopentyl)methanol (hereinafter also referred to as (1R ^* ,2R ^* ,3R ^* )-body); (1R ^* ,2S ^* ,3R ^* )-(2,3,4,4- Tetramethylcyclopentyl)methanol (hereinafter also referred to as (1R ^* ,2S ^* ,3R ^* )-body); (1R ^* ,2S ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol ( hereinafter also referred to as (1R ^* , 2S ^* , 3S ^* )-body); and (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-) represented by the following formula (4′) Tetramethylcyclopentyl)methanol (4') (hereinafter also referred to as (1R ^* ,2R ^* ,3S ^* )-isomer (4')). The (1R ^* ,2R ^* ,3S ^* )-body (4') has the same relative configuration as the OMB pheromone.

(In formula (4) above, bold bonds and hashed bonds represent relative configurations.)

As the (2,3,4,4-tetramethylcyclopentyl)methanol (4), racemic OMB pheromone (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl) Diastereomeric ratio (dr) of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate from the point of view of the production of methyl acetate (5A′) is 50% or more, (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol represented by the following formula (4') is preferred.

（上記一般式（５）中、Ｒ^２は水素原子又は炭素数１～１５の一価の炭化水素基を表す。） The (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5), which is the target substance in step D, is represented by the following general formula (5).

(In general formula (5) above, R ² represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 15 carbon atoms.)

Specific examples of the 2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) include (2,3,4,4-tetramethylcyclopentyl)methyl formate, (2,3,4 ,4-tetramethylcyclopentyl)methyl acetate, (2,3,4,4-tetramethylcyclopentyl)methyl propionate, (2,3,4,4-tetramethylcyclopentyl)methyl butyrate, (2,3, 4,4-tetramethylcyclopentyl)methyl pentanoate, (2,3,4,4-tetramethylcyclopentyl)methyl isobutyrate, (2,3,4,4-tetramethylcyclopentyl)methyl isovalate, (2,3 ,4,4-tetramethylcyclopentyl)methyl 3-methyl-3-butenoate, (2,3,4,4-tetramethylcyclopentyl)methyl tiglate, (2,3,4,4-tetramethylcyclopentyl)methyl = senecioate, (2,3,4,4-tetramethylcyclopentyl)methyl acrylate, (2,3,4,4-tetramethylcyclopentyl)methyl methacrylate and (2,3,4,4-tetramethylcyclopentyl) ) methyl 2-acetoxy-3-methylbutanoate and the like.

（上式中、Ａｃはアセチル基を示す。） Among the (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compounds (5), R ² in the above general formula (5) is a methyl group and is represented by the following general formula (5A) Since (2,3,4,4-tetramethylcyclopentyl)methyl acetate has the same planar structure as the sex pheromone of OMB, which is a major pest, it has a high industrial utility value.

(In the above formula, Ac represents an acetyl group.)

（上記式（５Ａ）中、Ａｃはアセチル基を示す。（Ｒ^＊）、（Ｓ^＊）、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表す。） Here, (2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A) represented by the planar structural formula of the OMB pheromone has four diastereomers. (1R ^* ,2R ^* ,3R ^* )-2,3,4,4-tetramethylcyclopentyl)methyl acetate (hereinafter also referred to as (1R ^* ,2R ^* ,3R ^* )-body) (1R ^* ,2S ^* ,3R ^* )-2,3,4,4-tetramethylcyclopentyl)methyl acetate (hereinafter also referred to as (1R ^* ,2S ^* ,3R ^* )-body);(1R ^* , 2S ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentyl)methyl acetate (hereinafter also referred to as (1R ^* ,2S ^* ,3S ^* )-body); Represented (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (hereinafter, (1R ^* ,2R ^* ,3S ^* )-body (5A') say). The (1R ^* ,2R ^* ,3S ^* )-body (5A') has the same relative configuration as the OMB sex pheromone.

(In formula (5A) above, Ac represents an acetyl group. (R ^* ), (S ^* ), bold bonds and hashed bonds represent relative configurations.)

（上式中の（Ｒ）、（Ｓ）、太線ウェッジ結合（ｂｏｌｄ ｗｅｄｇｅｄ ｂｏｎｄ）及びハッシュウェッジ結合（ｈａｓｈｅｄ ｗｅｄｇｅ ｂｏｎｄ）は絶対立体配置を表す。） Among (2,3,4,4-tetramethylcyclopentyl)methyl=acetate (5A), the (1R ^* ,2R ^* ,3S ^* )-form whose relative configuration is (1R ^* ,2R ^* ,3S ^* ) (5A') is a racemic form of OMB sex pheromone, and since it has already been confirmed to have OMB male attracting activity as described above, it has a very high industrial utility value.
The racemic form of the OMB pheromone is the following (1S,2S,3R)-(2,3,4,4-tetramethylcyclopentyl)methyl=acetate (1S,2S,3R)- (5A′) and its enantiomer (1R,2R,3S)-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (1R,2R,3S)-(5A′) means a 1:1 mixture with

((R), (S), bold wedged bond and hashed wedge bond in the above formula represent absolute configuration.)

Here, in the case of non-stereoselective synthesis, the expected value of the diastereomer ratio of the same (1R ^* ,2R ^* ,3S ^* )-isomer (5A') as the natural OMB pheromone in the resulting synthetic product becomes about 25% dr. In Non-Patent Document 1, which actually reports non-stereoselective synthesis, the diastereomer ratio of (1R ^* ,2R ^* ,3S ^* )-isomer (5A') is less than 20% dr. The three diastereomers other than the (1R ^* ,2R ^* ,3S ^* )-body (5A'), which account for 80% or more, have no activity against OMB, and the presence of a large amount of inactive components has some adverse effect in practice. There are concerns about the possibility of In addition, when the same amount of active ingredient is produced, for example, if the diastereomer ratio is halved, the total production amount is doubled, and a higher diastereomer ratio is more advantageous from the standpoint of industrial economy.
Therefore, 2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) is (2,3,4,4-tetramethylcyclopentyl)methyl= Acetate (5A) is preferred, and the diastereomer ratio (dr) of the (1R ^* ,2R ^* ,3S ^* )-isomer (5A') is preferably 50% or more, and 60% or more. more preferably 70% or more.

In the reduction step, as shown in the chemical reaction formula below, (2,3,4,4-tetramethylcyclopentyl)methanol (4) is converted to 2,3,4,4-tetramethylcyclopentyl as a substrate. Obtained by subjecting pentanecarbaldehyde (3) to a reduction reaction with a reducing agent.

A known reduction reaction from aldehyde to alcohol can be applied to the reduction reaction. The reduction reaction is usually carried out by reacting the substrate with a reducing agent in a solvent while cooling or heating as necessary.

Examples of the reducing agent in the reduction reaction include hydrogen; boron compounds such as borane, alkylborane, dialkylborane and bis(3-methyl-2-butyl)borane; dialkylsilane, trialkylsilane, hydrogenation Metal hydrides such as monoalkylaluminum and dialkylaluminum hydride; sodium borohydride, lithium borohydride, potassium borohydride, calcium borohydride, sodium aluminum hydride, lithium aluminum hydride, trimethoxyborohydride Complex hydride salts such as sodium, lithium trimethoxyaluminum hydride, lithium diethoxyaluminum hydride, lithium tri(tert-butoxy)aluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride and lithium triethylborohydride (complex hydride); and alkoxy or alkyl derivatives thereof, but using hydrogen or complex hydride salts for reasons such as ease of reaction conditions and/or workup and/or ease of product isolation. preferably.
When hydrogen is used as the reducing agent for the reduction reaction, the reaction can be carried out in the same manner as in the hydrogenation reaction of step C described above.

The case where a reducing agent other than hydrogen is used for the reduction reaction will be described in detail below.
The amount of the reducing agent used in the reduction reaction varies depending on the reducing agent used and/or the reaction conditions, etc., but generally the substrate 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3)1 It is preferably 0.1 mol to a large excess amount (2 mol to 500 mol), more preferably 0.2 mol to 8.0 mol, per mol.

Solvents in the reduction reaction include, for example, water; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; diethyl=ether, di-n-butyl=ether, diethylene glycol=diethyl=ether, diethylene glycol=dimethyl = ethers such as ether, tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, ethylene glycol = monomethyl = ether and diethylene glycol = monomethyl = ether; nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and n-butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide. mentioned.
The solvent may be used alone or in combination of two or more. Also, as the solvent, a commercially available one can be used.
As the solvent in the reduction reaction, an appropriate one can be selected and used depending on the type of reducing agent used. For example, preferred combinations of a reducing agent and a solvent include ethers; mixed solvents of ethers and alcohols; and mixed solvents of ethers and hydrocarbons when lithium borohydride is used as the reducing agent. and the like, and when lithium aluminum hydride is used as the reducing agent, ethers; , alcohols; mixed solvents of ethers and water; mixed solvents of hydrocarbons and water; and mixed solvents of ethers and alcohols.

The amount of the solvent used in the reduction reaction is preferably 0.01 parts by mass to 100,000 parts by mass with respect to 100 parts by mass of the substrate 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3). parts, more preferably 0.1 to 10,000 parts by mass.

The reaction temperature in the reduction reaction varies depending on the reagent and/or solvent used. -70°C to 20°C.
The reaction time in the reduction reaction can be set arbitrarily. from the point of view, and usually 0.5 to 100 hours is preferred.

Next, in the esterification step, (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) is converted into (2,3,4 ,4-Tetramethylcyclopentyl)methanol (4) is subjected to an esterification reaction. The reaction substrate (2,3,4,4-tetramethylcyclopentyl)methanol (4) is hereinafter referred to as the reaction substrate alcohol (4).

The esterification step includes known methods for producing esters, such as (i) reaction with an acylating agent, (ii) reaction with a carboxylic acid, (iii) transesterification reaction and (iv) substrate alcohol compound (4 ) into an alkylating agent, followed by reaction with a carboxylic acid.

(i) Reaction with an acylating agent The reaction with the acylating agent is carried out by reacting the reaction substrate alcohol (4) with the acylating agent and a base or an acid, sequentially or vice versa, or simultaneously. .

The reaction with the acylating agent may be carried out in solvent or without solvent.
Solvents used for the reaction with the acylating agent include, for example, chlorinated solvents such as methylene chloride, chloroform and trichlorethylene; hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; Ethers such as di-n-butyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and 1,4-dioxane; nitriles such as acetonitrile; ketones such as acetone and 2-butanone; ethyl acetate and esters such as n-butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide.
The solvent may be used alone or in combination of two or more. Also, as the solvent, a commercially available one can be used.

Examples of the acylating agent include carboxylic acid chloride, carboxylic acid bromide, carboxylic acid anhydride, carboxylic acid trifluoroacetic acid mixed acid anhydride, carboxylic acid methanesulfonic acid mixed acid anhydride, carboxylic acid trifluoromethanesulfonic acid mixed acid Anhydrides, carboxylic acid benzenesulfonic acid mixed acid anhydride, carboxylic acid p-toluenesulfonic acid mixed acid anhydride, carboxylic acid p-nitrophenyl acid anhydride, and the like.
The amount of the acylating agent to be used is 0.8 mol to 500 mol, preferably 0.8 mol to 50 mol, more preferably 0.8 mol to 5 mol, per 1 mol of alcohol (4) as a reaction substrate. is.

The bases preferably include triethylamine, diisopropylethylamine, N,N-dimethylaniline, pyridine and 4-dimethylaminopyridine.

In the reaction using an acylating agent such as an acid anhydride, the reaction can be carried out under an acid catalyst instead of the above bases.
Examples of the acid catalyst include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid; organic acids such as oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, iodine Zinc chloride, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin = dimethoxide, dibutyltin = oxide, titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium (IV) = ethoxide, titanium (IV) = Lewis acids such as isopropoxide and titanium (IV) oxide.
The amount of the base or the acid catalyst to be used is 0.0001 mol to 500 mol, preferably 0.001 mol to 50 mol, more preferably 0.01 mol, per 1 mol of alcohol (4) as a reaction substrate. mol to 5 mol.

As for the reaction temperature in the reaction with the acylating agent, an appropriate reaction temperature can be selected depending on the type of acylating agent used and/or the reaction conditions. ~100°C is more preferred.
The reaction time in the reaction with the acylating agent can be set arbitrarily, but the reaction is followed by gas chromatography (GC) and/or silica gel thin layer chromatography (TLC) or the like to complete the reaction. is desirable from the viewpoint of yield, and usually 0.5 to 100 hours is preferred.

(ii) Reaction with Carboxylic Acid The reaction with carboxylic acid is a dehydration condensation reaction between alcohol (4) as a reaction substrate and carboxylic acid, and is generally carried out in the presence of an acid.
The carboxylic acid is represented by the general formula ^R2COOH .
In the above formula, R ² is a hydrogen atom or a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 6 carbon atoms.
Linear saturated hydrocarbon groups such as methyl group, ethyl group, propyl group, n-butyl group, hexyl group and pentadecyl group as monovalent hydrocarbon groups for R ² ; isopropyl group, s-butyl group and isobutyl group , t-butyl and isohexyl branched saturated hydrocarbon groups; vinyl, allyl, 2-methylallyl, 1-propenyl, isopropenyl, 1-methyl-1-propenyl and 2-methyl A chain alkenyl group such as -1-propenyl group can be mentioned. Also, some of the hydrogen atoms of these hydrocarbon groups may be substituted with acyl groups having 1 to 6 carbon atoms, and specific examples include 1-acetoxy-2-methylpropyl groups. More specifically, the carboxylic acid includes formic acid, acetic acid, propionic acid, butyric acid, valeric acid, heptanoic acid, hexadecanoic acid, isobutyric acid, isovaleric acid, pivalic acid, methylheptanoic acid, acrylic acid, vinylacetic acid, and propenylacetic acid. , crotonic acid, methacrylic acid, tiglic acid, senecioic acid and 2-acetoxy-3-methylbutanoic acid.

The amount of carboxylic acid to be used is 0.8 mol to 500 mol, preferably 0.8 mol to 50 mol, more preferably 0.8 mol to 5 mol, per 1 mol of alcohol (4) as a reaction substrate. be.
Examples of the acid catalyst used for the reaction with the carboxylic acid include those similar to those for the reaction with the above (i) acylating agent.
The amount of the acid catalyst to be used is 0.0001 mol to 100 mol, preferably 0.001 mol to 1 mol, more preferably 0.01 mol to 0.5 mol, per 1 mol of alcohol (4) as a reaction substrate. It is a catalytic amount in moles. Examples of the solvent used for the reaction between the reaction substrate alcohol (4) and the carboxylic acid include those used for the reaction with the acylating agent.

As for the reaction temperature in the reaction with the carboxylic acid, an appropriate reaction temperature can be selected depending on the type of the carboxylic acid and/or the reaction conditions. preferable. A solvent containing hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene may be used to allow the reaction to proceed while azeotropically removing the resulting water out of the system. In this case, water may be distilled off while refluxing at the boiling point of the solvent under normal pressure, or water may be distilled off at a lower temperature under reduced pressure.
The reaction time in the reaction with carboxylic acid can be set arbitrarily, but the reaction can be completed by following the reaction using gas chromatography (GC) and/or silica gel thin layer chromatography (TLC) or the like. It is preferable from the viewpoint of yield, and usually 1 to 200 hours is preferred.

As another method for the reaction with carboxylic acid, a method is also possible in which the carboxylic acid is subjected to a condensation reaction with a condensing agent, and then the condensation reaction product and the reaction substrate alcohol (4) are subjected to condensation reaction under basic conditions. be.
The amount of carboxylic acid used in this alternative method is 0.8 mol to 500 mol, preferably 0.8 mol to 50 mol, more preferably 0.8 mol, per 1 mol of alcohol (4) as a reaction substrate. ~5 moles.
Examples of the condensing agent include N,N'-dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC·HCl); and O-(7-aza-1H-benzotriazol-1-yl)-N,N , N′,N′-tetramethyluronium hexafluorophosphate (HATU) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) and other uronium salts.
The condensing agent may be used alone or in combination of two or more. Moreover, a commercially available product can be used as the condensing agent.
The amount of the condensing agent to be used is 0.8 mol to 500 mol, preferably 0.8 mol to 50 mol, more preferably 0.8 mol to 5 mol, per 1 mol of alcohol (4) as a reaction substrate. is. Examples of bases include triethylamine, diisopropylethylamine, N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine and the like.
Solvents used in this alternative method include the same solvents as those used in the reaction with the acylating agent.

The reaction temperature in the alternative method can be appropriately selected depending on the type of carboxylic acid and/or the reaction conditions, but generally -50°C to the boiling point of the solvent is preferred, and room temperature to the boiling point of the solvent is more preferred. .
The reaction time in the alternative method can be set arbitrarily, but the reaction can be completed by following the reaction using gas chromatography (GC) and/or silica gel thin layer chromatography (TLC). from the point of view, and usually 0.5 to 100 hours is preferred.

（上記反応式中、Ｒはアルキル基を表し、Ｒ^２は上記の通りである。） (iii) Transesterification Reaction As shown in the reaction formula below, the transesterification reaction is carried out by reacting the reaction substrate alcohol (4) with an alkyl carboxylate (R ² COOR) in the presence of a reaction catalyst. , by removing the resulting alkyl alcohol (ROH).

(In the above reaction formula, R represents an alkyl group and ^R2 is as described above.)

The alkyl carboxylate is preferably a primary alkyl ester of carboxylate, particularly methyl carboxylate (R ² COOCH ₃ ), ethyl carboxylate (R ² COOCH ₂ CH ₃ ), n-propyl carboxylate (R ² COOCH ₂ CH ₂ CH ₃ ) is preferable from the viewpoint of price and/or easiness of reaction progress.
R ² in the general formula representing the primary alkyl ester of carboxylic acid is as defined for R ² in general formula R ² COOH in the above (ii) reaction with carboxylic acid.
The amount of the alkyl carboxylate to be used is 0.8 mol to 500 mol, preferably 0.8 mol to 50 mol, more preferably 0.8 mol to 5 mol, per 1 mol of alcohol (4) as a reaction substrate. Mole.
Examples of the catalyst used for the transesterification reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid; Acids; sodium = methoxide, sodium = ethoxide, potassium = t-butoxide and bases such as 4-dimethylaminopyridine; sodium cyanide, potassium cyanide, sodium acetate, potassium acetate, calcium acetate, tin acetate, aluminum acetate, aluminum acetoacetate and salts such as alumina; aluminum trichloride, aluminum = ethoxide, aluminum = isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride , zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium ( IV) = ethoxide, titanium (IV) = isopropoxide and Lewis acids such as titanium (IV) oxide may be mentioned.
The catalyst may be used alone or in combination of two or more. In addition, as the catalyst, a commercially available one can be used.
The amount of the catalyst to be used is 0.0001 mol to 100 mol, preferably 0.001 mol to 1 mol, more preferably 0.001 mol, which is a catalytic amount, per 1 mol of alcohol (4) as a reaction substrate. ~0.05 mol.

Examples of the solvent in the transesterification reaction include hydrocarbons such as hexane, heptane, benzene, toluene, xylene and cumene; diethyl ether, di-n-butyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether. , tetrahydrofuran and 1,4-dioxane.
The solvent may be used alone or in combination of two or more. Also, as the solvent, a commercially available one can be used.
Also, depending on the conditions of the transesterification reaction, the alkyl carboxylate itself, which is a reaction reagent, can be used as a solvent without using a solvent. In this case, it is advantageous in that extra operations such as concentration and/or solvent recovery are not required.

As for the reaction temperature in the transesterification reaction, an appropriate temperature can be selected depending on the type of alkyl carboxylate used and/or the reaction conditions. Particularly good results can be obtained by carrying out the reaction near the boiling point of methanol, ethanol, 1-propanol, etc. and distilling off the resulting lower alcohol. Alcohol may be distilled off at low temperature under reduced pressure.
The reaction time in the transesterification reaction can be set arbitrarily, but the reaction can be completed by following the reaction using gas chromatography (GC) and/or silica gel thin layer chromatography (TLC). It is preferable from the viewpoint of rate, and usually 1 to 200 hours is preferable.

(iv) A method of converting the alcohol (4) of the reaction substrate into an alkylating agent and then reacting it with a carboxylic acid Converting the alcohol (4) of the reaction substrate into an alkylating agent and then reacting it with a carboxylic acid In the process, for example, the reactant alcohol (4) is converted to the corresponding halide (chloride, bromide or iodide) or sulfonate (eg, methanesulfonate, trifluoromethanesulfonate, benzenesulfonate or p-toluenesulfonate, etc.). , these corresponding halides and carboxylic acids are reacted, usually in a solvent, under basic conditions. It is also possible to mix the reactant alcohol (4) with triphenylphosphine and diethyl azodicarboxylate and then react the mixture with the carboxylic acid, usually in a solvent.
Examples of the carboxylic acid include the same carboxylic acid used in the reaction with (ii) carboxylic acid.
The solvent, base, reaction time and reaction temperature used can be the same as those in the reaction between the reaction substrate alcohol (4) and the acylating agent. Carboxylate salts such as sodium carboxylate, lithium carboxylate, potassium carboxylate or ammonium carboxylate may be used instead of the combination of carboxylic acid and base.

Isolation and/or purification of (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) synthesized as described above can be carried out using conventional methods such as distillation under reduced pressure and/or various types of chromatography. Although it can be appropriately selected from purification methods in organic synthesis and used, distillation under reduced pressure is preferable from the viewpoint of industrial economy.

Prior to the reduction reaction step, 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) may be subjected to an isomerization reaction.
The isomerization step is an optional step and may be carried out if it is necessary to improve the trans-selectivity of the 1,2-position substituents.

One embodiment of the isomerization step includes the following chemical reaction formula.

^{( _ _} 1R ^* ,2R ^* ,3S ^* )-body (3″), and of the target compound (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5), OMB The object is to selectively synthesize racemic pheromone (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A').

Specifically, the chemical reaction ^formula is such that ( ^{1R *} ,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3″), the resulting (1R ^* ,2R ^* ,3S ^* )-2,3, By subjecting 4,4-tetramethylcyclopentanecarbaldehyde (3″) to a reduction reaction with a reducing agent, (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl ) obtaining methanol (4′), and subjecting the resulting (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′) to an esterification reaction thereby obtaining (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A'). As described above, since the isomerization reaction is an optional step, the above (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) It may be directly subjected to a reduction reaction without being subjected to a chemical reaction.

The isomerization step can be carried out, for example, by treating the substrate (1RS,2R ^* ,3S ^* )-isomer (3') under acidic or basic conditions. Aldehyde at position 1 of (1RS,2R ^* ,3S ^* )-form (3′) is capable of stereoisomerization by equilibration of the enol and aldehyde forms under acidic or basic conditions. Since it converges to a more stable configuration, the abundance ratio of the 1,2-trans (trans) form with less steric repulsion between the substituents at the 1 and 2 positions is improved, and (1R ^* , 2R ^* , 3S ^* ) - considered to give the body (3″).

The isomerization reaction can be carried out by mixing a substrate, an acid or base, and optionally a solvent. Also, the isomerization reaction may be carried out while cooling or heating.

The acid and the amount thereof suitably used when the isomerization reaction is carried out under acidic conditions are the same as the acid and the amount thereof used in the hydrolysis reaction of step B above.

The base preferably used when the isomerization reaction is carried out under basic conditions is the same as the base used in the step A of preparing the phosphorus ylide compound (7).
The amount of the base to be used can be set arbitrarily as long as a practically sufficient reaction rate is obtained. It is preferably 0.00001 to 10,000 mol, more preferably 0.0001 to 1,000 mol, still more preferably 0.001 to 100 mol.

In the isomerization reaction, the solvent, its amount, reaction temperature and reaction time that may be used are the same as the solvent, its amount, reaction temperature and reaction time used in the hydrolysis reaction of step B above.

When the (1R ^* ,2R ^* ,3S ^* )-isomer (3″) obtained in the isomerization reaction has sufficient purity for use in the next step, it can be used as a crude product or The liquid or the filtered reaction liquid may be used as it is in the next step.Alternatively, if it is desired to separate and remove impurities, an appropriate purification method in ordinary organic synthesis such as distillation and/or various chromatography may be selected. In the case of purification, distillation, for example, distillation under reduced pressure is particularly preferred from the viewpoint of industrial economy.

In the above isomerization reaction, (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A′) has a diastereomeric ratio (dr) of 50% or more. This is one reason why it is possible to

Next, the (1R ^* ,2R ^* ,3S ^* )-body (3″) obtained above is subjected to a reduction reaction with a reducing agent to obtain (1R ^* ,2R ^* ,3S ^* )-(2, 3,4,4-tetramethylcyclopentyl)methanol (4') is obtained.

Finally, (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′) obtained above is subjected to esterification to give a racemic OMB pheromone. (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A') is obtained.
(1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4') has a diastereomer ratio of 50% dr or more, whereby (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A′) has a diastereomeric ratio (dr) of 50% or more.

According to the production method of the present invention, among the four diastereomers of (2,3,4,4-tetramethylcyclopentyl)methyl acetate corresponding to the planar structural formula of the OMB pheromone, natural OMB pheromone The same (1R ^* ,2R ^* ,3S ^* )-isomer (5A') can be stereoselectively and easily produced with a selectivity of 50% or more dr. Further, by adjusting the reaction conditions, etc., it is possible to achieve 60% dr or more, 70% dr or more, 80% dr or more, and even 90% dr or more.

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples.
In the following, unless otherwise specified, "purity" indicates the area percentage obtained by gas chromatography (GC) analysis, and "production ratio" indicates the relative ratio of the area percentage obtained by GC analysis. .
"Yield" indicates the yield calculated based on the area percentage obtained by GC analysis.
In each example, reaction monitoring and yield calculation were basically carried out according to the following GC conditions.
GC conditions: GC apparatus: SHIMADZU GC-2014, capillary column: DB-5, inner diameter 0.25 mm × film thickness 0.25 μm × length 30 m, carrier gas: He, detector: FID, column temperature: 80°C → +5°C /min temperature rise, inlet: 230°C.
As the purity of raw materials, products and intermediates, values obtained by gas chromatography (GC) analysis are used and expressed as % GC.
Yield was calculated according to the following formula, taking into account the purity (% GC) of the starting material and product.
Yield (%) = {[(weight of product obtained by reaction x % GC)/molecular weight of product] ÷ [(weight of starting material in reaction x % GC)/molecular weight of starting material]} x 100 .
In addition, a "crude yield" means the yield calculated without refinement|purification.
Samples for spectral measurement of compounds were purified from crude products as necessary.
In the chemical structural formulas below, Me represents a methyl group, Ph represents a phenyl group, and Ac represents an acetyl group.

[Example 1]
Synthesis of 4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene (1A) (1: R ¹ = methyl group)

A mixture of 183 g of potassium tert-butoxide and 847 g of tetrahydrofuran was stirred under a nitrogen atmosphere with ice cooling, and 588 g of (methoxymethyl)triphenylphosphonium chloride was added and stirred for 100 minutes to give phosphorus ylide (7A) (7: R ¹ = methyl group ) was prepared. A mixture of 121 g (98.0% GC) of 2,3,4,4-tetramethyl-2-cyclopenten-1-one (6) and 480 g of tetrahydrofuran was added and stirred overnight. Evaporate the solvent, extract the solubles with hexane, and evaporate the hexane to obtain the crude product. Purification was carried out by distillation under reduced pressure, and 116 g (98.3% GC, yield 80%) of 4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene (1A) was separated from the exocyclic double bond. (boiling point 73-75° C./1.0 kPa).

4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene (1A)
Yellowish oil.
IR (D-ATR): ν=2954, 2928, 2862, 2830, 1705, 1668, 1461, 1376, 1358, 1328, 1251, 1223, 1135, 1090, 982, 802 cm ^-1 .
¹ H-NMR (500 MHz, CDCl ₃ ):
Major isomer (E form): δ = 0.96 (6H, s), 1.54 (3H, s), 1.58 (3H, d, J = 0.8 Hz), 2.21 (2H, d , J=2.3 Hz), 3.53 (3H, s), 5.98 (1H, tq, J=2.3, 0.8 Hz) ppm.
Minor isomer (Z form): δ = 0.93 (6H, s), 1.54 (3H, s), 1.79 (3H, d, J = 0.8 Hz), 2.13 (2H, d , J=1.5 Hz), 3.44 (3 H, s), 5.76 (1 H, tq, J=1.5, 0.8 Hz) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): E/Z geometric isomer mixture, δ=9.40, 9.64, 10.08, 13.16, 26.62, 27.25, 41.28, 42 .58, 43.81, 44.41, 59.08, 59.40, 122.26, 125.01, 127.56, 129.18, 136.64, 137.01, 143.19, 145.38 ppm .
GC-MS (EI, 70 eV): 29, 41, 53, 65, 77, 91, 105, 119, 136, 151, 166 (M+).

[Example 2]
Synthesis of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2)

20.0 g (98.3% GC) of 4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene (1A) obtained according to Example 1, 40 g of hexane, 40 g of tetrahydrofuran and 20% A mixture of 65 g of hydrochloric acid was stirred for 6 hours under a nitrogen atmosphere. The organic layer was separated and then worked up by normal separation washing and concentration to give the crude product. The crude product was purified by vacuum distillation to give 11.7 g (95.1% GC, 62% yield) of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) ( boiling point 61° C./0.45 kPa).

2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2)
Brownish oil.
IR (D-ATR): ν=2960, 2869, 2719, 1663, 1633, 1440, 1377, 1340, 1256, 1228, 1210 cm ^-1 .
¹ H-NMR (500 MHz, CDCl ₃ ): δ = 1.03 (3H, s), 0.97 (3H, d, J = 7.7 Hz), 8.72 (3H, s), 2.06 ( 3H, m), 2.25 (1H, m, *d, including J = 15.6Hz), 2.32 (1H, m, *d, including J = 15.6Hz), 2.35 (1H , m, *q, including J=7.7 Hz), 9.98 (1H, s) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): δ=11.86, 12.88, 23.25, 28.65, 39.89, 43.28, 55.53, 136.41, 165.40, 188 .70 ppm.
GC-MS (EI, 70 eV): 27, 41, 55, 67, 81, 95, 109, 123, 137, 152 (M+).

[Example 3]
2,3,4,4-tetramethylcyclopentanecarbaldehyde (3), ((1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) and (1RS ,2R ^* ,3R ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde)

11.3 g (88.4% GC) of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) obtained according to Example 2, 136 g of hexane and 1.35 g of 5% rhodium on carbon were pressurized. It was charged into a container (autoclave), filled with hydrogen gas, and stirred for 20 hours. The solid content was filtered off and the solvent was distilled off to give crude 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) 12.0 g (71.3% GC, crude yield 85%). obtained as an object. In addition, (1RS,2R ^* ,3S ^* )-form (3′) (same configuration as OMB pheromone for 2,3 positions)/(1RS,2R ^* ,3R ^* )-form (OMB for 2,3 positions) A steric configuration different from the sex pheromone) was found to be 96/4 according to GC analysis. The GC purity as (1RS,2R ^* ,3S ^* )-body (3') was 68.7% GC, and the crude yield was 82%.

2,3,4,4-tetramethylcyclopentanecarbaldehyde (3)
Yellowish oil.
IR (D-ATR): ν=2959, 2872, 2707, 1723, 1663, 1456, 1379 cm ⁻¹ .
GC-MS (EI, 70 eV): 29, 41, 55, 69, 83, 97, 98, 109, 123, 139, 154 (M+).

[Example 4]
Synthesis of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′)

(1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) obtained according to Example 3, 12.0 g (68.7% GC), tetrahydrofuran 50 g, 5 % caustic soda aqueous solution was stirred for 40 hours under a nitrogen atmosphere, then 10% sodium borohydride aqueous solution 10.1 g was added and further stirred for 2 hours. The reaction solution was diluted with hexane, the organic layer was separated, and then the usual work-up procedure by separation washing and concentration was performed to obtain a crude product. The crude product was purified by vacuum distillation to give 6.95 g (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′) (88.0% GC , yield 73%) was obtained (boiling point 91-92° C./1.0 kPa).

(1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′)
Colorless oil.
IR (D-ATR): ν=3329 (broad), 2955, 2872, 1459, 1386, 1377, 1053, 1005 cm ⁻¹ .
¹ H-NMR (500 MHz, CDCl ₃ ): δ = 0.78 (3H, d, J = 7.3 Hz), 0.86 (3H, s), 0.95 (3H, d, J = 6.9 Hz ), 0.97 (3H, s), 1.16 (1H, dd, J = 12.2, 9.6 Hz), 1.61 (1H, br.s), 1.64 (1H, dq, J = 9.2, 7.3 Hz), 1.68 (1H, dd, J = 12.6, 8.0 Hz), 1.81 (1H, m), 1.88 (1H, m), 3.52 (1H, dd, J=10.3, 7.3 Hz), 3.66 (1H, dd, J=10.3, 5.4 Hz) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): δ=10.24, 17.43, 23.86, 29.78, 38.62, 41.33, 44.50, 46.19, 48.20, 67 .47 ppm.
GC-MS (EI, 70 eV): 29, 41, 55, 69, 82, 97, 109, 123, 141, 154 (M+).

[Example 5]
Synthesis of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A')

6.45 g (88.0% GC) of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4') obtained according to Example 4, pyridine7. A mixture of 20 g and 6.30 g of acetic anhydride was stirred under a nitrogen atmosphere for 4 hours. Water and hexane were added, the organic layer was separated, and then normal separation washing and concentration work-up were performed to obtain a crude product. The crude product was purified by vacuum distillation to give (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A′) 7.48 g (88.6) % GC, yield 92%) (boiling point 87° C./0.87 kPa).
Diastereomeric ratio of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A') with the same relative configuration as the OMB sex pheromone by GC analysis was 92.8% dr.

(1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A')
Colorless oil.
IR (D-ATR): ν=2957, 2873, 1743, 1458, 1367, 1242, 1042, 970 cm ⁻¹ .
¹ H-NMR (500 MHz, CDCl ₃ ): δ = 0.78 (3H, d, J = 7.3 Hz), 0.85 (3H, s), 0.95 (3H, d, J = 6.9 Hz ), 0.97 (3H, s), 1.15 (1H, dd, J = 12.6, 9.2 Hz), 1.65 (1H, dq, J = 8.7, 7.3 Hz), 1 .67 (1H, dd, J = 12.6, 7.6 Hz), 1.87-1.97 (2H, m), 2.05 (3H, s), 3.99 (1H, dd, J = 10.7, 6.9 Hz), 4.06 (1H, dd, J = 10.7, 5.8 Hz) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): δ=10.22, 17.14, 21.02, 23.84, 29.73, 39.11, 41.28, 44.49, 44.52, 46 .2168.76, 171.35 ppm.
GC-MS (EI, 70 eV): 29, 43, 55, 69, 82, 97, 109, 123, 138, 154, 165, 178, 192.

[Example 6]
Synthesis of (2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A)

6.84 g of the crude product of 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) obtained according to Example 2 (78.0% GC, crude yield 88.9%), tetrahydrofuran 27 g and 0.38 g of 5% palladium on carbon were placed in a pressure vessel (autoclave), filled with hydrogen gas, and stirred for 18 hours. Solids were filtered off and then 15.4 g of 5% aqueous sodium hydroxide solution was added and stirred for 18 hours under nitrogen atmosphere. 7.3 g of a 10% sodium borohydride aqueous solution was added to the reaction mixture, and the mixture was stirred for 3 hours. The reaction solution was diluted with hexane, the organic layer was separated, and then the work-up procedure was carried out by conventional liquid separation washing and concentration to obtain (2,3,4,4-tetramethylcyclopentyl)methanol (4). of crude product was obtained. Subsequently, 7.59 g of pyridine and 5.88 g of acetic anhydride were added and stirred for 5 hours under nitrogen atmosphere. After stirring was completed, water and hexane were added, the organic layer was separated, and then normal liquid separation washing and post-treatment by concentration were carried out to obtain a crude product. The crude product was purified by vacuum distillation to give 5.87 g (90.4% GC) of (2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A) (bp 92-96°C). /1.1 kPa).
The yield from 4-(methoxymethylene)-1,1,2,3-tetramethyl-2-cyclopentene (1A) was 68%, 2,3,4,4-tetramethyl-2-cyclopentene-1 The overall yield from -one (6) was 55%.
Diastereomeric ratio of (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl=acetate (5A') having the same relative configuration as OMB sex pheromone from GC analysis was 78.1% dr.

(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A)
Colorless oil.
IR (D-ATR): ν=2956, 2872, 1743, 1455, 1366, 1242, 1042, 970 cm ⁻¹ .
¹ H-NMR (500 MHz, CDCl ₃ ): major isomer, δ=0.78 (3H, d, J=7.3 Hz), 0.85 (3H, s), 0.95 (3H, d, J = 6.9 Hz), 0.97 (3H, s), 1.15 (1H, dd, J = 12.6, 9.2 Hz), 1.65 (1H, dq, J = 8.7, 7. 3Hz), 1.67 (1H, dd, J = 12.6, 7.6Hz), 1.87-1.97 (2H, m), 2.05 (3H, s), 3.99 (1H, dd, J=10.7, 6.9 Hz), 4.06 (1H, dd, J=10.7, 5.8 Hz) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): major isomer, δ=10.22, 17.14, 21.02, 23.84, 29.73, 39.11, 41.28, 44.49, 44 .52, 46.2168.76, 171.35 ppm.
GC-MS (EI, 70 eV): 29, 43, 55, 69, 82, 97, 109, 123, 138, 154, 165, 178, 192.

[Comparative synthesis example]
(2S ^* ,3S ^* )-4-(methoxymethylene)-1,1 from (2R ^* ,3S ^* )-2,3,4,4-tetramethyl-2-cyclopenten-1-one (103) , 2,3-tetramethylcyclopentane (104) synthesis

1.35 g of potassium tert-butoxide was added to a mixture of 4.46 g of (methoxymethyl)triphenylphosphonium chloride and 10 g of tetrahydrofuran under nitrogen atmosphere while stirring under ice cooling. Stir for 20 minutes and then (2R ^* ,3S ^* )-2,3,4,4-tetramethyl-2-cyclopenten-1-one (103) 1.50 g (85.6% GC) and toluene A mixture of 10 g was added. The temperature was raised to room temperature and stirred for 10 hours. Water and diethyl ether are added, the organic layer is separated, and then the work-up operation is carried out by separation washing, filtration, drying, and concentration to obtain 4-(methoxymethylene)-1,1, as a crude product. 1.41 g of 2,3-tetramethylcyclopentane was obtained (75.8% GC, crude yield 63.5%).

In the resulting product, the methyl group at the 2-position of (2R ^* ,3S ^* )-2,3,4,4-tetramethyl-2-cyclopenten-1-one (103), which is a substrate, is epitified ( (2S ^* ,3S ^* )-body (104) produced by epimerization) followed by Wittig reaction, while having the same relative configuration as the OMB sex pheromone (2S ^* ,3R ^* ). The presence of the - form (104') could not be confirmed by GC-MS analysis.

For confirmation of the relative steric configuration, the reaction product was treated in accordance with Examples 2, 4 and 5 above to obtain (2,3,4,4-tetramethylcyclopentyl)methyl=acetate (5A). It was confirmed by converting to and comparing with the physical property data described in Non-Patent Document 3.

From the above results, if the production method of the present invention is applied, (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound, in particular, as a sex pheromone of OMB, which is an important agricultural pest, is predicted to occur. , (1R ^* , 2R ^* , 3S ^* )-(2,3,4,4-tetramethylcyclopentyl) methyl acetate, which is expected to be applied to pest control, is safer and safer than existing methods. It was shown that it can be produced efficiently, selectively and industrially, and has a very high industrial utility value.

The present invention relates to novel vinyl ether compounds. The present invention also provides aldehyde compounds, namely 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde and 2,3,4,4-tetramethylcyclopentanecarbaldehyde, and carboxylate compounds from said vinyl ether compounds. , ie, (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compounds.

J. Millar et al., J. Chem. Ecol. , 31, 2999 (2005) J. Millar et al., Tetrahedron Lett. , 48, 6377 (2007) J. Millar et al., Tetrahedron Lett. , 52, 4224 (2011) D. Reddy et al., Tetrahedron Lett. , 51, 5291 (2010) Bull. Soc. Chim. Fr. , 2981 (1970) J. Am. Chem. Soc. , 113, 8062 (1991)

（上式中、Ｒ^１は炭素数１～１５の一価の炭化水素基を表し、波線はＥ体、Ｚ体又はそれらの混合物であることを表し、太線結合（ｂｏｌｄ ｂｏｎｄ）及びハッシュ結合（ｈａｓｈｅｄ ｂｏｎｄ）は相対立体配置を表す。）

(In the above formula, R ¹ represents a monovalent hydrocarbon group with 1 to 15 carbon atoms, the wavy line represents the E form, Z form or a mixture thereof, bold bond and hash bond hashed bond) represents the relative configuration.)

Considering the reaction formula of the above retrosynthetic analysis, the chemical reaction formula according to one embodiment of the present invention is shown as follows.

（上記一般式中、Ｒ^１は炭素数１～１５の一価の炭化水素基を示す。Ｐｈはフェニル基を表す。波線は、Ｅ体、Ｚ体又はそれらの混合物であることを表す） [2] Step A
The process A for obtaining the vinyl ether compound represented by the following general formula (1) will be described below. The vinyl ether compound (1) comprises 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and the following formula ( It is obtained by subjecting phosphorus ylide compound (7) represented by 7) to Wittig reaction.

(In the general formula above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms. Ph represents a phenyl group. A wavy line represents an E form, a Z form or a mixture thereof.)

R ¹ in general formula (101) is as defined in general formula (1) above. X is a halogen atom, preferably a chlorine atom, a bromine atom or an iodine atom. Specific examples of the triphenylphosphonium halide compound (101) include (methoxymethyl)triphenylphosphonium chloride, (methoxymethyl)triphenylphosphonium bromide, (methoxymethyltriphenylphosphonium)iodide, and (ethoxymethyl)triphenylphosphonium chloride. , (butoxymethyl)triphenylphosphonium chloride, (pentadecyloxymethyl)triphenylphosphonium chloride, (isopropoxymethyl)triphenylphosphonium chloride, (cyclohexyloxymethyl)triphenylphosphonium chloride, (allyloxymethyl)triphenylphosphonium chloride , (phenoxymethyl)triphenylphosphonium chloride, (benzyloxymethyl)triphenylphosphonium chloride, triphenyl[2-(trimethylsilyl)ethoxymethylene]phosphonium chloride, [(2-methoxyethoxy)methyl)triphenylphosphonium chloride, [2 -(methylthio)ethoxymethyl)triphenylphosphonium chloride, [(4-chlorophenoxy)methyl)triphenylphosphonium chloride and [(4-methoxyphenoxy)methyl)triphenylphosphonium chloride and the like.
As the triphenylphosphonium halide compound (101), a commercially available one may be used, or a quaternary phosphonium reaction between a halide represented by the following general formula (102) and triphenylphosphine (PPh ₃ ) may be prepared.

In order to preferentially produce the (1RS,2R ^* ,3S ^* )-body (3'), the hydrogenation catalyst is a metal such as rhodium or palladium, a metal oxide containing these metals, or a metal oxide containing these metals. A catalyst or a metal oxide catalyst supported on a carrier such as carbon, alumina, zeolite or silica gel is preferably used, and carbon is particularly preferred. Specifically, rhodium = carbon, palladium = carbon and palladium hydroxide = carbon. It is even more particularly preferred to use In general, in the hydrogenation reaction using these hydrogenation catalysts, hydrogen atoms are easily added from the sterically vacant surface of the substrate molecule. , 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) is hydrogenated preferentially from the more open face, ie, the face opposite the 3-methyl group, to give the desired 2,3- It is believed that the cis configuration is preferentially obtained. In addition, since the relative configuration of the 2,3-dimethyl group of the (1RS,2R ^* ,3S ^* )-body (3′) obtained in step C is maintained until the final product in the subsequent steps, step C It is very important to improve the diastereomeric ratio of the target product to increase the stereoselectivity at .

Specific examples of the 2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) include (2,3,4,4-tetramethylcyclopentyl)methyl formate, (2,3,4 ,4-tetramethylcyclopentyl)methyl acetate, (2,3,4,4-tetramethylcyclopentyl)methyl propionate, (2,3,4,4-tetramethylcyclopentyl)methyl butyrate, (2,3, 4,4-tetramethylcyclopentyl)methyl pentanoate, (2,3,4,4-tetramethylcyclopentyl)methyl isobutyrate, (2,3,4,4-tetramethylcyclopentyl)methyl isovalerate, (2,3 ,4,4-tetramethylcyclopentyl)methyl 3-methyl-3-butenoate, (2,3,4,4-tetramethylcyclopentyl)methyl tiglate, (2,3,4,4-tetramethylcyclopentyl)methyl = senecioate, (2,3,4,4-tetramethylcyclopentyl)methyl acrylate, (2,3,4,4-tetramethylcyclopentyl)methyl methacrylate and (2,3,4,4-tetramethylcyclopentyl) ) methyl 2-acetoxy-3-methylbutanoate and the like.

(ii) Reaction with Carboxylic Acid The reaction with carboxylic acid is a dehydration condensation reaction between alcohol (4) as a reaction substrate and carboxylic acid, and is generally carried out in the presence of an acid.
The carboxylic acid is represented by the general formula ^R2COOH .
In the above formula, R ² is a hydrogen atom or a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 6 carbon atoms.
Linear saturated hydrocarbon groups such as methyl group, ethyl group, propyl group, n-butyl group, hexyl group and pentadecyl group as monovalent hydrocarbon groups for R ² ; isopropyl group, s-butyl group and isobutyl group , t-butyl and isohexyl branched saturated hydrocarbon groups; vinyl, allyl, 2-methylallyl, 1-propenyl, isopropenyl, 1-methyl-1-propenyl and 2-methyl A chain alkenyl group such as -1-propenyl group can be mentioned. Also, some of the hydrogen atoms of these hydrocarbon groups may be substituted with acyl groups having 1 to 6 carbon atoms, and specific examples include 1-acetoxy-2-methylpropyl groups. More specifically, the carboxylic acid includes formic acid, acetic acid, propionic acid, butyric acid, valeric acid, heptanoic acid, hexadecanoic acid, isobutyric acid, isovaleric acid, pivalic acid, methylheptanoic acid, acrylic acid, vinylacetic acid, and propenylacetic acid. , crotonic acid, methacrylic acid, tiglic acid, senecioic acid and 2-acetoxy-3-methylbutanoic acid.

(iv) A method in which alcohol (4) as a reaction substrate is converted into an alkylating agent and then reacted with a carboxylic acid In a method in which alcohol (4) as a reaction substrate is converted into an alkylating agent and then reacted with a carboxylic acid , for example, converting the reactant alcohol (4) into the corresponding halide (chloride, bromide or iodide) or sulfonate (eg, methanesulfonate, trifluoromethanesulfonate, benzenesulfonate or p-toluenesulfonate, etc.), The corresponding halide and carboxylic acid are reacted, usually in a solvent, under basic conditions. It is also possible to mix the reactant alcohol (4) with triphenylphosphine and diethyl azodicarboxylate and then react the mixture with the carboxylic acid, usually in a solvent.
Examples of the carboxylic acid include the same carboxylic acid used in the reaction with (ii) carboxylic acid.
The solvent, base, reaction time and reaction temperature used can be the same as those in the reaction between the reaction substrate alcohol (4) and the acylating agent. Carboxylate salts such as sodium carboxylate, lithium carboxylate, potassium carboxylate or ammonium carboxylate may be used instead of the combination of carboxylic acid and base.

(1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A')
Colorless oil.
IR (D-ATR): ν=2957, 2873, 1743, 1458, 1367, 1242, 1042, 970 cm ⁻¹ .
¹ H-NMR (500 MHz, CDCl ₃ ): δ = 0.78 (3H, d, J = 7.3 Hz), 0.85 (3H, s), 0.95 (3H, d, J = 6.9 Hz ), 0.97 (3H, s), 1.15 (1H, dd, J = 12.6, 9.2 Hz), 1.65 (1H, dq, J = 8.7, 7.3 Hz), 1 .67 (1H, dd, J = 12.6, 7.6 Hz), 1.87-1.97 (2H, m), 2.05 (3H, s), 3.99 (1H, dd, J = 10.7, 6.9 Hz), 4.06 (1H, dd, J = 10.7, 5.8 Hz) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ): δ=10.22, 17.14, 21.02, 23.84, 29.73, 39.11, 41.28, 44.49, 44.52, 46 .21, 68.76, 171.35 ppm.
GC-MS (EI, 70 eV): 29, 43, 55, 69, 82, 97, 109, 123, 138, 154, 165, 178, 192.

Claims (11)

a step of obtaining 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde represented by the following formula (2) by subjecting a vinyl ether compound represented by the following general formula (1) to a hydrolysis reaction; A method for producing 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2), comprising at least

(In general formula (1) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and the wavy line represents the E form, Z form, or a mixture thereof.) The method for producing 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) according to claim 1, and the 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2 ) to a hydrogenation reaction to obtain 2,3,4,4-tetramethylcyclopentanecarbaldehyde represented by the following formula (3): Method for producing methylcyclopentanecarbaldehyde (3).

The method for producing 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) according to claim 2, and reducing the 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) a step of obtaining (2,3,4,4-tetramethylcyclopentyl)methanol represented by the following formula (4) by subjecting it to a reduction reaction with an agent, and the (2,3,4,4-tetramethyl and obtaining a (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound represented by the following general formula (5) by subjecting cyclopentyl)methanol (4) to an esterification reaction. , (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5).

(In general formula (5) above, R ² represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 15 carbon atoms.) The (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) is (2,3,4,4-tetramethylcyclopentyl)methyl acetate represented by the following formula (5A) , in the (2,3,4,4-tetramethylcyclopentyl)methyl acetate, among the four diastereomers, (1R ^* ,2R ^* ,3S ^* )- represented by the following formula (5A') (2,3,4,4-tetramethylcyclopentyl) according to claim 3, wherein the diastereomeric ratio (dr) of (2,3,4,4-tetramethylcyclopentyl)methyl acetate is 50% or more. A method for producing a methyl carboxylate compound (5).

(In formulas (5A) and (5A′) above, Ac represents an acetyl group, (R ^* ), (S ^* ), bold bonds and hashed bonds represent relative configurations. ) 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) is represented by the following formula (3′) (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentane is carbaldehyde, and by subjecting the (1RS,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3′) to an isomerization reaction, the following formula (3″) obtaining (1R ^* ,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde represented by
The reduction reaction is carried out using the obtained (1R ^* ,2R ^* ,3S ^* )-2,3,4,4-tetramethylcyclopentanecarbaldehyde (3″) to obtain (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′) is obtained,
The esterification reaction is carried out using the (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methanol (4′) obtained above to obtain the (1R ^* ,2R ^* ,3S ^* )-(2,3,4,4-tetramethylcyclopentyl)methyl acetate (5A′) is obtained.
5. The method of claim 4.

By subjecting 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and a phosphorus ylide compound represented by the following general formula (7) to a Wittig reaction , The method for producing 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde (2) according to claim 1, further comprising the step of obtaining said vinyl ether compound (1).

(In general formula (7) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and Ph represents a phenyl group.) By subjecting 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and a phosphorus ylide compound represented by the following general formula (7) to a Wittig reaction , The process for producing 2,3,4,4-tetramethylcyclopentanecarbaldehyde (3) according to claim 2, further comprising the step of obtaining said vinyl ether compound (1).

(In general formula (7) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and Ph represents a phenyl group.) By subjecting 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and a phosphorus ylide compound represented by the following general formula (7) to a Wittig reaction 4. The method for producing (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) according to claim 3, further comprising the step of obtaining said vinyl ether compound (1).

(In general formula (7) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and Ph represents a phenyl group.) By subjecting 2,3,4,4-tetramethyl-2-cyclopentenone represented by the following formula (6) and a phosphorus ylide compound represented by the following general formula (7) to a Wittig reaction 5. The method for producing (2,3,4,4-tetramethylcyclopentyl)methyl carboxylate compound (5) according to claim 4, further comprising the step of obtaining said vinyl ether compound (1).

(In general formula (7) above, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and Ph represents a phenyl group.) A vinyl ether compound represented by the following general formula (1).

(In the formula, R ¹ represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and the wavy line represents the E form, Z form or a mixture thereof.) 2,3,4,4-tetramethyl-1-cyclopentenecarbaldehyde represented by the following formula (2).